Download The Interface Between Borderline Personality and Bipolar II Disorders

The Interface Between Borderline Personality and Bipolar II Disorders
Tarique Perera, Carola Formica, Marissa Miyazaki, Michele Insanally, Rachel Hensel
Department of Psychiatry, New York State Psychiatric Institute and College of
Physicians and Surgeons, Columbia University Medical Center, New York NY 10032
Correspondence and requests for materials should be addressed to [email protected]
Abstract
Mood disorders with affective lability constitute a cluster of syndromes with many
overlapping factors. Among these, borderline personality disorder (BPD) and bipolar II
(BPII) are the most prevalent. In this extensive review, the commonalities and differences
between BPD and BPII are summarized from three perspectives: (a) phenomenology
including symptoms, course, and comorbid illnesses, (b) etiology including early
environment, genetics, and biology, and (c) treatment including pharmacology and
psychotherapy. Although the literature reveals many phenomenological attributes shared
by BPD and BPII key etiological differences exist, implying that the two conditions are
distinct entities. The divergent etiological factors require divergent treatment approaches
for each disorder. This review offers practical guidelines for dissecting subtle
phenomenological differences that contrast BPD from BPII and appropriately tailoring
treatment to optimize therapeutic outcome.
Introduction
There are several areas in modern psychiatry where empirical observations
suggest that DSM-IV diagnostic classification constructs merit clarification. Where
disorders across the multi-axial system seem to correspond clinically or to co-occur
frequently, the integrity of Axis I and Axis II distinctions requires re-evaluation.
Comorbidity of Axis I and Axis II disorders has been an important focus of psychiatric
literature and research over the past 15 years. This issue is especially true in the case of
Bipolar II Disorder (BPII) and Borderline Personality Disorder (BPD).
Our
understanding of these two disorders suggests a definite clinical overlap, an interface that
bears more than academic significance, as it may have significant implications for
treatment. A question arises: are these two disorders distinct and hence separable or are
they presentations of a single syndrome, making separation arbitrary? The categorical
and multi-axial approach espoused in the DSM-IV supports the notion that these two
disorders are separate entities with merely incidental overlaps in phenomenology. By
considering BPII as an Axis I disorder the DSM views it as a cycle of transient mind
states that are genetically determined and biologically driven. By considering BPD as an
axis II disorder, the DSM views it as an enduring set of pathological traits that are
behaviorally ingrained. Research in the past 10 years has given rise to a more unifying
hypothesis that considers BPD a sub-affective illness belonging in a single 'soft bipolar'
continuum with BPII (Akiskal 1994). The dimensional approach (Tuinier and Verhoeven
1995) raises a third possibility, that BPII and BPD might be related only in certain
aspects, such as affective instability, and unrelated in others, such as learned behaviors
(Soloff, Lis et al. 1994).
Methods
In this study, the interface between BPD and BPII were evaluated with methods
similar to those employed previously, (Gunderson, J. G. and K. A. Phillips 1991) where
hypothetical possibilities for a relationship between two disorders were generated and
then the hypotheses were evaluated by reviewing the literature on the two disorders.
Based on the available literature three hypotheses concerning the relationship were
generated by the authors:



Hypothesis I: BPD and BPII are distinct disorders that share artifactual
overlapping criteria due to the limitations of our current definitions, but have
no true biological links.
Hypothesis II: BPD and BPII are separate disorders but are linked to each
other in some descriptive and biological aspects.
Hypothesis III: BPD and BPII are variants of a single disorder.
These hypotheses were reviewed within the domains of phenomenology, etiology, and
treatment. Under the domain of phenomenology, the symptoms and signs of these
disorders were evaluated. Computer-based searches limited to the Med Line system were
used for each disorder with a special reference to the few studies that directly compared
the two disorders.
PHENOMENOLOGY
The phenomenology of psychiatric disorders involves symptoms and signs as well
as associated ego defenses and psychic conflicts. Individual symptoms and signs can be
evaluated within the context of four dimensions, i.e., cognitive abnormalities, affective
instability, impulsivity, and anxiety that are thought to bridge Axis I and II disorders
(Siever and Davis 1991). Since anxiety is an affective state we collapsed the domain of
phenomenology into abnormalities of cognition, affect (including anxiety), and
impulsivity.
A. Cognition
1. Attention
Both BPI (Faraone, Biederman et al. 1997) (Geller, Zimerman et al. 2000)
(Wozniak, Biederman et al. 1995) (West, McElroy et al. 1995) (Neuchterlein, Dawson et
al. 1991) (Sax, Strakowski et al. 1995) (Serper 1993) and BPD (Fossati, Novella et al.
2002; Dowson, McLean et al. 2004) (Sax, Strakowski et al. 1995) are associated with a
high incidence of attention related deficits. Many of the bipolar patients with attention
problems have BPII (Wilens, Biederman et al. 2003) and among these patients attention
problems are more common with patients who have borderline stigmata, such as early
onset of illness, (Sachs, Baldassano et al. 2000) rapid cycling (Akiskal, Hantouche et al.
2003), and treatment resistance (Martinez-Aran, Vieta et al. 2004), (Strober, DeAntonio
et al. 1998). Furthermore, both these disorders are often preceded by childhood
diagnoses of ADHD. Among all patients with Axis II disorders, those with childhood
ADHD are more likely to be diagnosed with BPD or Antisocial Personality Disorder
(Fossati, Novella et al. 2002; Dowson, McLean et al. 2004). When compared to patients
with other mood disorders, those with BPII are more likely to have attentional problems
during childhood (Akiskal, Maser et al. 1995). Thus, impairments in attention appear to
be a common thread shared by these two disorders. While cognitive deficits in BP appear
to be limited to attention (Harmer, Clark et al. 2002), borderline patients have additional
cognitive impairments in perceptual speed, working memory (Stevens, Burkhardt et al.
2004), non-verbal executive function and non-verbal memory, (Dinn, Harris et al. 2004)
and depression (Burgess 1991). These impairments seem to be continuously present in
BPD patients (Kremers, Spinhoven et al. 2004).
2. Dissociation
Among patients with personality disorders, dissociation symptoms are most
prevalent in BPD patients (Zanarini 2000). These symptoms are not prevalent in BPII
patients. Compared to BPII, Borderlines had stronger evidence of childhood physical and
sexual trauma, maternal neglect (Brodsky, Cloitre et al. 1995; Van Den Bosch, Verheul et
al. 2003) and self-injurious behavior, which in turn predicted significantly higher scores
on the Dissociative Expression Scale (van der Kolk, Perry et al. 1991).
3. Psychosis
Psychotic symptoms have been reported in a minority of BPII patients, many of
whom were in the depressed phase (Lewis L. Judd). Clear-cut delusions, hallucinations
and other 'true' psychotic symptoms are rare among Borderlines (Pope, Jonas et al. 1985;
Links, Steiner et al. 1989; Zanarini, Gunderson et al. 1990). Patients with BPD have high
rates of “micro” psychotic episodes that involve odd thinking, dissociative symptoms,
and non-delusional paranoia (van Reekum, Conway et al. 1993). In addition to BPDs,
certain patients with major depression also exhibit micro-psychotic symptoms (Links,
Steiner et al. 1989; Nishizono-Maher, Ikuta et al. 1993). Therefore, in theory, BPD and
BPIIs who are in the depressed phase may share similar micro-psychotic symptoms. In
contrast, hypomania by DSM-IV definition lacks psychosis. In one study, the grandiosity
and irritability seen during hypomanic episodes (Pavuluri, Herbener et al. 2004) were
thought to resemble micro-psychotic symptoms. However, because these BPIIs tended
to be rapid cyclers (Perugi, Toni et al. 2003) with an early onset of symptoms
(McGlashan and Heinssen 1988) and poorer inter-episode functioning (Cannon, Jones et
al. 1997), they displayed characteristics of borderline patients . It is fair to assume that
micro-psychotic symptoms are fairly specific to BPD that help distinguish the disorder
from BPII.
B. Affect
Affective instability, defined as a predisposition to marked and rapidly reversible
shifts in affective state (Siever and Davis 1991), is a hallmark of both cluster B
personality disorders such as BPD and mood disorders such as BPI, BPII, cyclothymia,
and dysthymia (Coccaro and Kavoussi 1991). This prominent symptom often leads to
confusion in differentiating BPII from BPD. Affective lability in BPIIs differs from that
in borderlines in terms of the quality of affect, duration of mood episodes, and triggers of
episodes.
1. Quality of Affect
Although the symptom of affective lability is common to BPII and BPD and
responsive to similar medications, it differs in terms of the quality of affective mood
shifts (Henry, Mitropoulou et al. 2001).
Hypomania
In terms of affect, the most distinguishing feature that separates BPII from BPD is the
presence of euphoria during hypomanic episodes in BPIIs and the absence of sustained
euphoria in BPDs. In a direct prospective comparison of the two disorders, BPII patients
cycled into hypomania with an elated mood whereas patients with BPD did not exhibit
elation (Henry, Mitropoulou et al. 2001). The equivalent of a hypomanic episode in BPD
surfaces as anxiety, (Koenigsberg, Harvey et al. 2002) anger, and impulsivity (Coccaro
and Kavoussi 1991). It is important to differentiate the impulsivity, hostility and/or selfdestructive “pseudohypomania” seen in Borderlines from the euphoric hypomania of
BPIIs (Henry, Mitropoulou et al. 2001). For instance, the French multi-center national
EPIDEP study described two groups of BPII patients with two different versions of
hypomania—the ‘classic’ driven-euphoric type and the irritable risk-taking type. While
euphoric hypomania correlated with BPII, irritable risk-taking hypomania correlated with
cyclothymic temperament (Hantouche, Angst et al. 2003).In a companion study, the latter
was associated with borderline traits such as intense and unstable course, as well as
comorbid Axis II features including histrionic and passive aggressive behavior (Akiskal,
Hantouche et al. 2003).
Depression
Major and minor depressive episodes tend to predominate the course of both BPD
(PerryJ.C. 1992) (Bunce SC 1999) and BPII, (Lewis L. Judd 2003, Benazzi, F. 2000) and
depressive episodes in both disorders tend be of the atypical subtype (Akiskal, Hantouche
et al. 2003) (Perugi, Toni et al. 2003) with irritability as a prominent feature (Coid 1993)
(Akiskal and Benazzi 2005). However, key differences exist. Depression with
melancholic features has been reported in BPII patients (Benazzi 2004), whereas
depression in BPDs is exhibited as a stable pattern of disrupted behavior with frequent
depressive symptoms that include (Coid 1993) (Rogers, Widiger et al. 1995) emptiness,
loneliness, and abandonment fears (Rogers, Widiger et al. 1995). Moreover, while most
BPII patients display discrete major depressive episodes, BPD patients suffer from
chronic symptoms (PERRY 1985) with frequent exacerbations that are shorter in duration
than the typical major depressive episode. Such episodes resemble recurrent brief
depression (RBD) (Montgomery, Montgomery et al. 1990), a subtype of depression
described in ICD-10 (World Health Organization, 1992).
Anxiety
High rates of panic attacks have been reported in BPD (Akiskal 1994) and BPII (Lewis L.
Judd 2003), and many BPII patients with comorbid panic are misdiagnosed as BPII
(Savino N 1993). Anxiety related symptoms are more prevalent among Borderlines than
patients with other personality disorders (Bunce SC 1999) (Comtois, Cowley et al. 1999)
and tend to be higher in BPIIs than patients with other mood disorders (Henry, Van den
Bulke et al. 2003) (Sasson, Chopra et al. 2003). However, in one direct longitudinal
comparison, anxiety symptoms were more prevalent and more chronic in BPDs when
compared to BPIIs (Perry 1985). In a cross sectional study of mood episodes, BPD
patients were far more likely to shift from depression to anxiety than BPIIs (Henry, C
2001). Theoretically, anxiety symptoms in BPIIs are thought to stem from defense
mechanisms related to isolation, undoing, and intellectualization (Perry and Cooper
1986); (Siever and Davis 1991), whereas anxiety in BPD stems from pessimistic worry in
anticipation of future problems and passive avoidant behaviors (Svrakic, Whitehead et al.
1993) (Perry and Cooper 1986); (Siever and Davis 1991). High rates of anxiety may be
common to both disorders, leading to confusion in diagnosis (Savino 1993), but
borderlines appear to have more intense and persistent symptoms stemming from
different triggers and defenses.
Anger
Anger and irritability appear to be more significant in both BPD (Henry, Mitropoulou et
al. 2001) and BPII (Henry, Mitropoulou et al. 2001) (Perlis, Smoller et al. 2004) than in
unipolar depression, but borderline patients have greater levels of anger that may stem
from primitive forms of object relations and a propensity for greater impulsivity
(Leichsenring 2004).
2. Triggers of Affective Episodes
Affective disturbances in borderline patients are thought to be triggered by
interpersonal conflicts (Koenigsberg, Harvey et al. 2001) borne of fears of abandonment
and intolerance of loneliness (Gunderson 1996). In three longitudinal studies, stressful
life events were more likely to influence the course of BPD than bipolar II, other
personality disorders (Pagano ME 2004, PerryJ.C. 1992), or major depression (Pagano
ME 2004). The interpersonal sensitivity characteristic of BPDs is also seen among BPIIs
who are more likely to have depression with atypical features that result in mood
reactivity and interpersonal sensitivity (Benazzi and Rihmer 2000; Perugi, Toni et al.
2003). In multiple studies, environmental stress appears to precede the initial and early
bipolar mood episodes while later episodes appear to be autonomously triggered,
suggesting a kindling phenomenon. Stressful environmental antecedents are more
common in late onset bipolar patients with no family history (Johnson, AnderssonLundman et al. 2000) (Ellicott, Hammen et al. 1990); (Ramana and Bebbington 1995).
However, all studies that have addressed this issue looked at mixed populations of bipolar
I and II and were mostly retrospective. Thus, it is not known whether interpersonal stress
is a trigger or a consequence of bipolar episodes.
3. Duration of Affective Episodes
Affective lability is a hallmark of both disorders. However, in a direct
comparison, Borderlines exhibited more mood lability than BPIIs and BPIIs had greater
lability than those with other personality disorders (Henry, Mitropoulou et al. 2001).
This greater lability in BPDs may stem from differences in the duration of mood cycles.
Mood changes in BPDs are believed by some to occur within hours (Coccaro and
Kavoussi 1991) throughout the course of the day (Cowdry, Gardner et al. 1991), whereas
by DSM-IV definition the minimum length of a mood cycle in BPII is 4 days. Even
when more relaxed criteria for episode duration were used, the modal distribution for the
length of a BPII mood episode was at least one day (Akiskal 1996). When hypomanic
episodes of less than four days were considered in two separate studies, approximately
half of BPII patients met criteria for comorbid cyclothymic temperament (Akiskal,
Hantouche et al. 2003). These patients were significantly more likely to meet criteria for
borderline personality disorder or show stigmata of BPD, such as rejection sensitivity
(Perugi, Toni et al. 2003), unstable course (Akiskal, Hantouche et al. 2003), suicidality,
and female gender (Coryell, Solomon et al. 2003). It is likely that BPII patients who
meet criteria for cyclothymia essentially belong to the “borderline” realm and can be
differentiated from BPIIs who meet strict DSM-IV criteria for mood episodes that are
four days or longer. Therefore, the length of mood episodes is a distinguishing feature
between these two disorders.
4. Inter-Episode Functioning
Depressive episodes tend to predominate the course of BPD and BPII. In one direct
comparison, depressive symptoms were episodic in BPII individuals and chronic in BPD
(Perry, J. C. 1985). This pattern was also evident in more detailed prospective studies that
examined BPD and BPII course separately. In the BPD studies there were no symptom
free periods, whereas 75% of BPII patients were symptom free of strict DSM-IV mood
episodes (Coryell, Keller et al. 1989) (Benazzi 2000) and more than 45% were free of all
symptoms. It is likely that most of the BPII patients with poor inter-episode functioning
have comorbid cyclothymia, which as stated earlier shares features with BPD (Akiskal,
Hantouche et al. 2003). Therefore, the presence of discrete mood episodes with good
inter-episode functioning may distinguish “pure” BPIIs that meet strict DSM-IV criteria
from both BPDs and BPII patients with borderline features. This generalization is less
applicable to older borderlines because the chronicity of symptoms tends to dissipate
after approximately the first decade of BPD diagnosis.
C. Behavior
1. Impulsivity
Impulsivity appears to be a common feature in both BPD (Pukrop 2002) and
Bipolar Disorder (Swann, Pazzaglia et al. 2003) but it differs in terms of quality and
triggers. Qualitatively, BPD patients have greater levels of impulsivity than those with
BPII (Henry, Mitropoulou et al. 2001) (Akiskal, Hantouche et al. 2003). Impulsivity
seems to predict the diagnosis of BPD, discriminate borderlines from normal controls
(Fossati, Barratt et al. 2004) (Links, Heslegrave et al. 1999), and distinguish BPIIs with
borderline features (cyclothymic BPIIs) from non-cyclothymic BPIIs (Akiskal,
Hantouche et al. 2003). Compared to BPIIs, the impulsive behavior in BPDs and
cyclothymic BPIIs appears to be associated with greater levels of aggression (Henry,
Mitropoulou et al. 2001) and irritability (Akiskal, Hantouche et al. 2003); (Hantouche,
Angst et al. 2003). In contrast, impulsive behavior in BPIIs was associated with more
"carefree, uninhibited and stimulus seeking" (Akiskal 1994). The triggers of impulsive
actions seem to differ between the two groups. Although inter-episode impulsivity is
higher in BPII than BPI (Engstrom 2004), this behavior is generally considered to be a
state phenomenon in BPII associated with autonomous hypomanic episodes (Akiskal &
Mallya, 1987; (Akiskal 1994) (Perugi, Toni et al. 2003). In contrast, impulsivity in
Borderline PD is a trait symptom often triggered by interpersonal events (Koenigsberg,
Harvey et al. 2001). This symptom was stable for at least seven years in a longitudinal
prospective follow-up study of BPD (Links, Heslegrave et al. 1999). In a direct
comparison of the two disorders, trait measures of impulsiveness as assessed by the
Barrat Impulsiveness Scale were significantly higher in patients with BPD compared to
those with BPII and other personality disorders. The diagnosis of BPII did not affect BIS
scores and did not differ from those of controls (patients with PDs other than BPD)
(Henry, Mitropoulou et al. 2001).
2. Suicide
A high incidence of negative outcomes in BPD and BPII can be traced to poor
impulse control. A recent study by Fossati et al confirmed that impulsive aggression was
an important factor in the recurrent suicidal behavior of BPD patients (Fossati, Barratt et
al. 2004); (Henry, Mitropoulou et al. 2001); (Koenigsberg, Harvey et al. 2001). Suicidal
behavior is reported to occur in up to 84% of patients with BPD, with a mean of 3.4
lifetime attempts per individual. Suicide completion is an infrequent event among BPD
patients. Approximately 10% of BPD patients in follow-up studies successfully commit
suicide.
Although there are no direct comparisons, the rates of completed suicides appear
to be greater in BPIIs than BPDs. There is no difference in the rates of suicide attempts
between BPIIs and BPIIs with borderline features (Akiskal, Hantouche et al. 2003).
Personality variables such as harm avoidance (HA) and low persistence (PS) have also
been identified as risk factors for suicidal attempts among Bipolar (I and II) patients, as
well as lower age of onset, gender (female), and family history of suicide (Engstrom,
Brandstrom et al. 2004). This same study found that patients with suicide attempts and
family history of suicide had more anticipatory worry, fatigability and asthenia
(Engstrom, Brandstrom et al. 2004). In their study of the prevalence and disability of
bipolar spectrum disorders in the U.S. population through a reanalysis of the ECA
database, Judd et al (2003) found that the suicide attempt rate in hypomanic subjects
(Bipolar II) was quite high, with a lifetime prevalence of 34%, higher than the 24% seen
in manic subjects (Bipolar I) (Judd and Akiskal 2003). The quality of affective instability
has also been correlated with intense inappropriate anger and suicidal threats, gestures,
and attempts (Koenigsberg, Harvey et al. 2001). Chronic suicidal ideation is an ongoing,
semi-chronic process that typically emerges within an Axis II context. The nature of
suicidal symptoms in BPD is seemingly more about the urgency to contain overwhelming
feelings prompted by relationship issues, such as anger, rather than a genuine intent to
end life. Among Borderlines, parasuicidal gestures like self-cutting function as means of
affective regulation ( Paris J. 2004). A number of psychological functions underlie selfharm behavior, including regulating intense affect, coping with overwhelming feelings of
loneliness or anger, eliciting caring responses from others, and consolidating a consistent
identity that is founded on self-destructive behavior.
3. Self-Harm
Deliberate self-harm is defined as the intentional injuring of one’s own body
without apparent suicidal intent (Pattison and Kahan 1983). Other names for this
behavior include superficial moderate self-mutilation (Favazza and Rosenthal 1993), selfinjurious behavior, parasuicide and self-wounding. Deliberate self-harm typically begins
in adolescence and involves numerous episodes and a variety of methods, including
cutting, burning, slashing, banging, picking and bone breaking (Favazza et al, 1989).
Skin cutting appears to be the most common form of self-harm, occurring in at least 70%
of individuals who deliberately harm themselves (Herpetz, 1995, (Briere and Gil 1998)).
Repeated self-harm is one of the operational criteria for Borderline Personality disorder
in the DSM classification (American Psychiatric Association, 1994). In a longitudinal
study conducted using 480 patients, a total of nine out of ten patients had some
personality disturbance, 42% of these with disorder. For those where information on
parasuicide events was collected, the proportion having a repeat episode ranged from
33% to 63% for different personality disorders. Those with BPD were most likely to
repeat episodes quickly, with a mean of 89 days for 25% to repeat (Tyrer et al., 2004).
Individuals with Borderline Personality disorder are at high risk for nonsuicidal
self-injury or parasuicidality (Gerson and Stanley 2002). In a study using 1,986 military
recruits, 62% of whom were men, approximately 4% of the participants reported a history
of deliberate self-harm. Compared to participants without a history of deliberate selfharm, self-harmers scored higher on self and peer-report measures of borderline,
schizotypal, dependent, and avoidant personality disorder symptoms and reported more
symptoms of anxiety and depression (Klonsky et al., 2003). It is apparent from the
literature that parasuicide and self-injurious behavior are significantly higher in BPD
patients than in BPIIs. Self-mutilation has been found to occur in 70-80% of patients
who meet DSM-IV criteria for Borderline Personality disorder (Bohus, Limberger et al.
2000). Histories of childhood sexual and physical abuse are highly significant predictors
of self-cutting and other self-injurious behaviors. In a longitudinal study of self-harm in
personality disorders and Bipolar II disorder, borderline personality pathology was
significantly associated with cutting and other self-injurious behavior. Antisocial,
schizotypal, and narcissistic personality disorders and Bipolar II disorder were not
significantly related to any of the self-destructive behavior. The subjects with the most
severe histories of childhood separation, neglect and sexual abuse continued being selfdestructive later in life. Hence, childhood trauma contributes to the initiation of selfinjurious behavior, but lack of secure attachments helps maintain it (Van der Kolk, 1991).
In a comparison of self-injury in Borderline Personality disorder, Major
Depression and Chronic Paranoid Schizophrenia, borderline patients showed more selfinjurious behaviors and more chronic depressive symptoms than the major depression or
schizophrenia groups (Burgess 1991). Among Borderlines, parasuicidal gestures like
self-cutting function as means of affective regulation (Paris 2004). Thus, patients with
Borderline Personality disorder exhibit greater levels of self-injurious behavior than
BPIIs that may stem from childhood histories of trauma, where patients react to current
stresses as a return of childhood trauma, neglect and abandonment.
4. Interpersonal Relationships
Evidence from multiple studies of personality disorders suggests that severe
relationship dysfunction is the key biomarker of Borderline Personality Disorder
(Gunderson JG, Lyons-Ruth K, 2008). Borderline patients are unable to function in an
organized or adaptive way across various interpersonal domains, including work, love
and parenting (Hill J, Pilkonis P, Morse J, et al 2008). Their maladaptive social behavior
results in part from a reduced capacity for mentalization, or the awareness of one’s
perception of self and other as a reflection of one’s own personal biases rather than a true
depiction of reality (Bateman A, Fonagy P 2007). Because of this limited reflective
ability, patients are often unable to regulate their emotions or perceive themselves or
others in anything but extreme, absolute terms (Gregory FJ, Remen AL, Soderberg M, et
al. 2009); (Lynch TR, Trost WT, Salsman N, et al. 2007).
The strong emotions of borderline individuals are usually time-limited reactions
to real or imagined abandonment that disappear upon the perceived return of a
caregiver’s nurturance (Bornstein et al. 2010). Borderlines show a deficit in the capacity
to acknowledge loving and hostile feelings toward the same person simultaneously
(object constancy). This can lead to a defense known as “splitting,” where that person is
either idealized or devalued (Delgado S, Songer D 2009.) According to Kernberg (1986),
Splitting protects the wholeness of the ego without integrating bad object and subject
images into their own perceptions about themselves. Whereas the affective state of BPDs
is often dictated by external factors such as interpersonal sensitivity, in BPIIs it tends to
be autonomous, driven by persisting mood states (Fiedorowwicz & Black). For example,
an analysis of MBTI profiles in hospitalized bipolar patients showed that the manic
patients were more often extroverted types when compared with depressive individuals
(62% vs. 30%), who showed fewer social interactions with friends and family (Bisbee et
al. 1982).
Insecurity prompted by an intense fear of abandonment is another hallmark of
BPD that helps to distinguish it from BPII (Fiedorowicz JG, Black DW 2010).
According to various interpersonal theorists, unstable relationships in Borderlines stem
from the conflict between their need for unconditional love and their fear of intimacy
(Freeman, Pretzer, Fleming & Simon 2004). This central ambivalence may be rooted in
the belief that others secretly value their neediness, but that an open expression of
dependency would result in exploitation, abandonment, or loss of self-identity (Benjamin
1993). Self-reports from borderline patients verify that BPD is more strongly associated
with maladaptive dependent traits like enmeshment and neediness than with healthy traits
like connectedness (Bornstein & Languirand 2003). Aside from enmeshment, studies of
the defensive functioning of 73 patients meeting DSM-III criteria for borderline found
that Borderlines employed manipulative defense mechanisms such as acting out, passive
aggression, and splitting (Perry & Cooper 1986) in their interpersonal relationships.
While BPIIs’ insecure attachments may give the illusion of splitting, they are
typically brought on by internal mood states that cause them to withdraw from
relationships rather abandonment fears (Fiedorowwicz & Black). High reactivity,
emotionality, suicidality, and mood instability (for which the borderline label is often
invoked), are strongly marked by cyclothymic BP-II, particularly in its soft, ultra-rapid
and mixed expressions (Akiskal, 1996, 2004);(Perugi et al., 2004);(MacKinnon and Pies,
2006). Studies by Perugi et al. suggest that reactivity in AD (a marker of BPII) is
subserved by cyclothymia; such patients are likely to be high on interpersonal sensitivity.
The interpersonal burden that a cyclothymic temperament invokes may either detract
from a caregiver’s support or lead to criticism, hostility, and over-involvement, all of
which are associated with greater likelihood of depression relapse in treated individuals
(Butzlaff & Hooley, 1998).
5. Defense Mechanisms
Among BPDs there is documentation of poor functioning between mood episodes
(Benazzi 2000) that is likely to stem from a borderline ‘temperament’ involving high
scores on harm avoidance and impulsivity (Joyce, Mulder et al. 2003); Svrakic, 1993;
(Pukrop 2002)). Incidences of these two traits are significantly higher than in bipolar
patients in studies that directly compare the two disorders (Henry, Mitropoulou et al.
2001). According to Joyce et al, a combination of childhood abuse and/or neglect, a
borderline temperament consisting of high novelty seeking and high harm avoidance,
childhood/adolescent depression, hypomania, conduct disorder and alcohol/drug
dependence are all contributory factors to the development of BPD (Joyce, 2003).
Phenomenology Summary
As noted previously, individual symptoms and signs can be evaluated within the
context of four dimensions thought to bridge Axis I and II disorders (Siever et al.):
cognitive abnormalities, affective instability, impulsivity and anxiety, which, as an
affective state, can be collapsed into abnormalities of cognition, affect and impulsivity.
Aspects of these four dimensions also contribute to disrupted interpersonal functioning in
both BPDs and BPIIs.
Both BPII and BPD are associated with a high incidence of attention related
deficits (Faraone et al.). Moreover, dissociative symptoms are prevalent in BPD patients
but, to the best of our knowledge, have not been reported in BPII patients. Psychotic
symptoms have been reported in a minority of BPII patients, many of whom were in the
depressed phase. Clear-cut, ‘true’ psychotic symptoms are rare among Borderlines (Pope
et al.), who instead have high rates of “micro” psychotic episodes that involve odd
thinking, dissociative symptoms and non-delusional paranoia (Van Reekum et al.).
Affective lability in BPIIs differs from that in BPDs in terms of the quality of
affect, duration of mood episodes and triggers of episodes. In terms of affect, the most
distinguishing feature that separates BPII from BPD is the presence of euphoria during
hypomanic episodes in BPIIs and the absence of sustained euphoria in BPDs, for whom
the equivalent of a hypomanic episode is anxiety, anger and impulsivity (Coccaro et al.)
Depressive episodes tend to predominate the course of both disorders, but emptiness,
loneliness and abandonment fears characters BPD (Rogers et al.) while “atypical”
depressive features such as mood reactivity, interpersonal sensitivity, increased appetite,
and hypersomnia are more predictive of ultimate bipolar outcome in patients who have
not previously experienced an episode of hypomania (Perugi G, Akiskal HS, Lattanzi L,
Cecconi D, Mastrocinque C, Patronelli A, et al. 1998). The episodes, moreover, are
chronic in BPDs but episodic in BPIIs. Irritability and affective lability are common in
both disorders but BPDs have greater levels of anger and more mood lability than BPIIs.
Smith et al. posits that an underlying cyclothymic temperament may be responsible for a
broad clinical phenotype covering the diagnoses of atypical depression, bipolar disorder,
and BPD (Perugi G, Akiskal HS 2002).
Impulsivity appears to be a common feature in both disorders. However, in BPD
the trait seems to be associated with greater levels of aggression and irritability and is
often triggered by interpersonal events, whereas in BPIIs it is instead associated with
more “carefree, uninhibited and stimulus seeking” and hypomanic episodes (Akiskal).
Suicidal behavior is reported to occur in up to 84% of patients with BPD, although the
rates of completed suicides appear to be greater in BPIIs than BPDs. Patients with BPD
exhibit greater levels of self-injurious behavior than BPIIs that may stem from childhood
histories of trauma.
Extreme relationship dysfunction represents an overlap in phenomenology for
BPD and BPII. In Borderlines, relationship difficulties are directly linked to childhood
abandonment and the development of primitive defense mechanisms (Gunderson 1996).
BPDs have the ability to create strong dependencies (enmeshment) by using manipulative
behavior to gain concern from others (Presniak, Olson, MacGregor 2010). As victims of
repeated abuse they have not emotionally experienced object constancy in early
relationships, so they often resort to maladaptive modes of regulating their emotions,
such as splitting, projective identification and idealization/devalulation (Kernberg 1986).
Splitting, in particular, is used to protect the wholeness of the ego without integrating bad
object/subject images into Borderlines’ perceptions of themselves (Ibid.)
Interpersonal sensitivity is also prevalent among BPIIs in whom atypical
depression results in affective lability (Benazzi and Rihmer 2000; Perugi, Toni et al.
2003). However, repeated angry outbursts, suicide attempts, or acts of deliberate selfharm that are reactions to interpersonal stress and reflect extreme rejection sensitivity are
hallmarks of BPD. (Gunderson, Weinberg, Daversa, et al. 2006) In the presence of
these symptoms, the diagnosis of bipolar disorder is unlikely or secondary (Ibid.)
Moreover, while attachment disorganization has a causal relationship to BPD, it remains
unclear whether interpersonal stress is a trigger or a consequence of BPII. Given the
significant social impairment in youths with bipolar disorder (Geller et al., 2000),
particularly after onset of the illness (Quackenbush et al., 1996), the association between
relationship stress and mania may be a recursive one in which the most disturbed youths
generate the highest levels of peer-related stress, and in turn exacerbates their mood
lability. (Eunice Y. Kim, Ph.D., David J. Miklowitz, Ph.D., Adrine Biuckians, M.A., and
Kimberley Mullen, M.A. 2007)
ETIOLOGY
A. Environmental
Clinical theories and retrospective data show that experiences of severe
relationship adversity, abuse, and deficits in validating experiences characterize the
childhood backgrounds of borderline adults, who might otherwise have grown up with a
healthy self-esteem and the ability to trust others (Linehan M 1993); (Bateman A, Fonagy
P 2006). One study showed emotional denial by a male caretaker and inconsistent
treatment by a female caretaker as significant risk predictors of BPD. An extrapolation of
that study found patients with BPD were significantly more likely to report having
caretakers of both sexes deny the validity of their thoughts, fail to provide them with
protection, neglect their physical care, withdraw from them emotionally and treat them
inconsistently (Zanarini 1997). There is also evidence that BPD patients misinterpret
past events as trauma (Baily 1999).
Parental withdrawal in infancy and separation in the first five years of life - a
period highly sensitive with respect to the development of emotion regulation skills - is
seen as an especially important early risk factor for BPD in adulthood (Siever and Steele
2010.) According to a report by Crawford et al. on 750 families (representative of the
U.S. population) who were followed from infancy until adulthood, children who were
exposed to early maternal separation had elevated levels of BPD symptoms from
adolescence to middle adulthood, independent of current maternal problems,
temperament, child abuse, and parenting risks (Crawford TN, Cohen PR, Chen H, et al
2009). Conversely, among prepubertal and early-adolescent bipolar patients, low
maternal warmth was temporally associated with more rapid recurrences of manic
episodes (Geller, et al., 2004).
Children as young as three years old have been shown to organize around the goal
of controlling interactions with their caregiver, increasing a dysfunctional parent’s
involvement by means of coercion, humiliation, or even flattery ((Moss, Parent, Gosselin,
Rousseau, & St. Laurent 1993.) cWhile disorganized attachments in early childhood may
not be uniquely related to BPD, longitudinal prospective studies have shown a strong link
between disorganization and disturbed forms of social relating later in life for borderline
patients (Carlson EA 1998.) Traumatic experiences encountered in early development
can suspend personality development at the stage in which the traumatic event occurred
(Massie & Szajnberg, 2006; Spates, Waller, Samaraweera & Plaisier, 2003) and cause
defense mechanisms of that stage to persist despite their inappropriateness (Cramer &
Block, 1998; Finzi-Dottan & Karu, 2006). These defenses can in turn lead to difficulties
expressing one’s needs and wishes to others (passive aggression), projecting internal
selves onto others (projection), and ego splitting, which involves a devaluation of the self
(TAS) (Perry & Cooper 1986.) As a result of a maladapted ego, Borderlines often look to
others to mitigate malformations in their "wholeness" and "uniqueness" related to
deficiencies in coping with stressful life events (SLE) (Ausubel, 1996; Steinwald, 1994).
The basic motivation for their interpersonal behavior is the recreation of the chaotic
emotional environment with the primary caregiver who was absent during early
experiences (Balint 1992).
The “kindling-sensitization” theory (Post, 1992) suggests that a stressful life event
is also required to trigger Bipolar Disorder. However, while childhood maltreatment
directly informs disrupted relationships in adult BPDs (Linehan M 1993), no studies are
currently available that look specifically at BPII and childhood trauma, and patients with
BPI are less likely to have a history of trauma than patients with other mood disorders
(ANAES- YEAR?) Non-traumatic life stress such as suicide of a mother or sibling, and
less significantly the death of a family member, unemployment, divorce or recent
marriage (Kessing, 2004) have been associated with the initiation of manic or mixed
episodes (Kennedy, 1983; Ellicott, 1990; Hunt, 1992) in some studies while others have
failed to find any relationship (Chung, 1986; Sclare, 1990). One possible reason for this
discrepancy is the idea that BPI and II patients belong to two subsets. While one group
has a strong familial history with an autonomous and early onset of illness, the second
group lacks history, with an onset of stress-induced symptoms appearing later in life
(ADD Johnson, 2000 Ramana, 1995) (Johnson, Andersson-Lundman et al. 2000)
(Ellicott, Hammen et al. 1990); (Ramana and Bebbington 1995)). When differentiating
BPD from BPII, an autonomous or non-traumatic, stress-mediated onset of illness points
to BPII, whereas reports on childhood trauma or neglect, whether perceived or real,
suggest BPD.
B. Genetic Risk Factors
There is significant evidence to support the genetic inheritance of BPD and BPII.
Patients with BPII have a high twin concordance rate (78% in MZ) (Benazzi 2004)
(Joyce, Doughty et al. 2004) and more first-degree relatives with BPII than BPI. Studies
also suggest that adoptees carry the same risk for BP as their biological relatives.
Chromosomal linkage studies of bipolar disorder points to a multi-gene, specifically,
18p11.2, 18q22, 21q21, 4p16, and Xq26 (Berrettini 1998), non-Mendelian inheritance
with an environmental contribution (Ginns 1996). Borderline patients also show a twin
concordance rate (35% among MZ and 7% among DZ) (Torgersen, Lygren et al. 2000)
and family history (Loranger, Oldham et al. 1982) (Zanarini, Frankenburg et al. 1988)
(Baron, Gruen et al. 1985) of BPD. However, family history studies should be regarded
with caution because they introduce the confounding variable of environment.
In an attempt to resolve the gene-environment question, Gunderson and LyonsRuth proposed that a genetic temperament involving distress proneness in infancy
constitutes a vulnerability factor, which under conditions of non-optimal care or abuse
may evolve into BPD (2008). While evidence for inheritability of BPD is not as strong
as that for Bipolar II (Siever, Torgersen et al. 2002), the evidence for a genetic basis is
stronger for various dimensions of BPD, such as impulsivity and affective instability
(Silverman, Pinkham et al. 1991), than it is for the disorder as a whole. Impulsivity, for
example, has been shown to be heritable based on twin and adoption studies. It may be
related to reduced serotonergic modulation of key cortical inhibitory areas, resulting in a
loss of the normal inhibition of aggressive acts, such as self-harm, suicide, and violence
towards others (Smith et al. 2004). Though a paucity of research exists on affective
instability in BPDs, one study suggests that it may be caused by an abnormality in the
cholinergic systems of the paralimbic areas responsible for depressive response, which
correlates directly with the severity of affective –instability traits in BPDs (Baumann B,
Bogerts B, 2001.)
In Borderlines certain genetic factors have been shown to directly modulate
interpersonal sensitivity. The 7-repeat DRD4 allele, for instance, may code for an
increased biological sensitivity to context under adverse conditions, such as unresolved
mourning regarding past loss (Boyce and Ellis 2005.) The likelihood of an abused child
developing borderline traits such as depression and avoidance may also be influenced by
the “s” allele of 5-HTTLPR, a serotonin transporter gene associated with the
development of depression in individuals with histories of maltreatment or recent
stressful events (Caspi et al 2003). The presence of the short allele has been linked to
augmented response in the amygdala (Hairiri & Holmes, 2006) and increased release of
the stress hormone cortisol in response to separation in animal studies (Barr et al., 2004).
It also appears to involve the broad affective instability of the soft bipolar spectrum
reflected in limbic hyperactivity (Hariri et al. 2002).
Borderline and cyclothymic BPII patients both seem to share the serotonin
transporter gene “s” allele (Gonda et al., 2006; Ni et al., 2006), but beyond that little
evidence exists that points to a genetic linkage between BPD and bipolar disorders. At
least three studies have failed to show an increase in BPD in the families of BP probands
(Coryell, Akiskal-YEAR?). Examination from a dimensional perspective has been more
conclusive though (Silverman- YEAR?), as affective lability (Benazzi 2004) and
depression (Joyce, Doughty et al. 2004) appear to run in the families of both BPII and
BPD patients. However, when BPD probands with comorbid depression were excluded,
no increased risk for depression was observed (Pope-YEAR?). Cyclothymia has been
shown to occur more often in families of BPs when compared to controls. Howland
speculates that cyclothymics can be divided into two sub-groups: one with a history of
BP that responds well to treatment and another without history of BP that responds
poorly to treatment (Howland, Akiskal, Peselow). Cyclothymia in the former group could
be a precursor to BPII and in the latter, a variant of BPD.
Interestingly, social support was found to moderate depression risk in patients
with both a history of abuse and the presence of the “s” allele of 5-HTTLPR (Kaufman et
al 2004). The DRD4 polymorphism, linked to a risk for attachment disorganization and
interpersonal sensitivity, also acts as a marker of high responsiveness toward therapeutic
intervention. (Bakermans-Kranenburg MJ, van IJzendoorn MH, Pijlman FTA, et al.
2008) Risk for attachment disorders in maltreated children is thus modified by both
genetic and environmental factors, with social support as one of the most important
elements promoting resilience –even in the face of a genetic predisposition toward
psychiatric illnesses.
Familial increase in impulsivity and affective instability may affect the proband’s
early environments. Adoption studies are needed to determine if high genetic
concordance in BPDs is the result of a common environment or an authentic inheritance
pattern. If so, an inherited unstable affective temperament can lead to BPII but
development while BPD would require a second, environmentally-induced trigger.
C. Biology
Various brain imaging studies have proven inconclusive in etiological studies of
Borderline Personality Disorder. A recent PET study found an association between
memories of childhood abuse in female BPD patients and increased blood flow to the
dorsolateral prefrontal cortex, an area responsible for remembering people who are
absent, and less blood flow to the anterior cingulate, an area governing the brain’s ability
to conduct complex assessments (Schmahl, 2004). However, while several PET studies
showed significant prefrontal and frontal hypometabolism in medial orbital frontal cortex
areas among BPD patients (Soloff, 2003; De la Fuente, 1997), others showed significant
hypermetabolism in those same areas (Juengling, 2003).
Several
studies
of
Borderlines have found reductions in both hippocampal volume (Driessen, 2000; Tebartz,
2003; Schmahl, 2003; Rush, 2003; Brambilla, 2004) and amygdala volume (Tebartz,
2003; Schmahl, 2003). In one such study, the reduction in hippocampal volumes was
most marked in subjects who had experienced childhood abuse (Brambilla, 2004).
Increased activity in the amygdala of patients with BPD compared with controls has also
been shown (Herpertz, 2001; Donegan, 2003).
The underlying neurobiology of Bipolar Disorder remains largely unknown, but
many researchers believe that it arises from modulations of synaptic and neural plasticity
in critical circuits mediating affective and cognitive functioning (Martinowich et al.
2009). Functional neuroimaging studies have shown abnormalities in the brains of BPDs
indicative of dysfunction in key neural circuits distributed through the amygdala, the
PFC, anterior cingulate, medial thalamus, and related regions of the basal ganglia
(Carlson et al. 2006.) For example, Stoll et al. demonstrated decreased activity of the
prefrontal cortex in bipolar patients during depression (Stoll, 2000) while other studies
have identified a loss of network connectivity in prefrontal white matter (Adler 2004 and
prefrontal reductions in gray matter volume (Frangou S et al. 2002).
Among BPDs, most studies have found that TSH blunting is due to concurrent
affective disorders (Weston &Seiver). Only rapid cycler BPs show hypothyroidism
(Bauer 1994) and loss of TSH surge during sleep (Sack 1988).
Those who develop BPD have higher premorbid histories of conduct disorders
(Sullivan). While a childhood history of ADHD has been associated with both BPD and
BP diagnosis, Singh et al argue that ADHD symptoms represent an early manifestation of
pediatric onset BP in certain at risk individuals (Singh, 2006). Furthermore, Akiskal et al.
found that temperamental measures of mood lability and energy-activity served as
powerful predictors of BPII switching among depressed patients who were unipolar at
entry (Akiskal, Maser et al. 1995).
Finally, both BPs and BPDs a show decrease in 5-HIAA and prolactin response to
fenfluramine challenge. In BPDs, low 5-HIAA correlated with suicidality, and decreased
prolactin response correlated with increased impulsivity, anger, and self-damaging acts
(Coccaro, 1989) (Paris, 2004). There has been conflicting evidence regarding the exact
role that serotonin plays in BPD. It has been shown that there is increased 5HT2A
receptor binding in BPD independent of impulsivity and that differences in impulsivity
can be related to polymorphism in this gene (Soloff 2007) (Nomura 2006). However, one
study showed that this receptor was only related to extraversion in BPD patients and not
to impulsivity or BPD itself (Ni 20.06). Furthermore, adrenergic and cholinergic
hypersensitivity, present in both groups, results in affective instability (Coccaro) (Siever
1991). Dopamine has been shown to be correlated with micro psychotic episodes and
may play a role in BPD (Blacker).
D. Conclusion
Childhood trauma and neglect have been shown to predispose BPD. Among
patients with BPD experiences of early life trauma are common, but a far more
significant number of patients report feelings of neglect or parental indifference in the
absence of overt trauma. Therefore, perception of neglect during childhood is a more
sensitive indicator of borderline pathology. This is of consequence in the treatment
setting where fears of abandonment or rejection can interfere in the patient-provider
relationship.
In contrast, genetic inheritance appears to be stronger in patients with BPII and
may help differentiate bipolars from borderline patients. Borderline patients do show
evidence of inheritability regarding the separate and specific dimensions of BPD,
particularly impulsivity and affective instability, the former being an inheritance pattern
that overlaps with BPII. Overall, the genetic contribution is significantly greater in BPII,
whereas with BPD, temperament constitutes a vulnerability factor, which under nonoptimal conditions may evolve into disorganized attachments and later BPD.
The data on biological/medical factors contributing to these disorders is
conflicting and therefore inconclusive. Many of the studies pertaining to BP including
structural deficits did not differentiate between I and II. Certain subgroups of patients
with soft neurological signs or neurochemical abnormalities such as increased 5HT
turnover seem to be predisposed to certain dimensional aspects that are either common to
both disorders such as mood dysregulation and or more specific to one of the disorders
such as impulsivity. Despite an increasing number of biological studies, the mechanisms
by which these disorders lead to the associated symptoms are currently unknown.
Prior Psychiatric History/Comorbidities
Two demographic studies have shown that compared to OPDS, BPD is femaledominated, with an earlier onset than other personality disorders (peak rates at 19-34
years) (Weissman). While average age of onset for BPII is 21.6 years, the highest risk
ages for onset are 15-19 years in both BPI and BPII. A possible male predominance
among BPs has been challenged by retrospective studies that found an even gender ratio
(Ramana, Weissman, Weiss).
In a prospective 10 year study of 641 youth those that developed BPD were found
to have marked conduct disorders, aggression, depression, and immaturity based on
maternal and self-reported behavior problems (Kutcher Check-YEAR?). Another study
showed that major depressives with comorbid BPD had significantly higher premorbid
histories of conduct disorders than pure major depressives or major depressives with
comorbid OPDs (Sullivan-YEAR?). History of childhood ADHD has been shown to be
associated with BPD diagnosis (Fossati, Novella et al. 2002). Early age at first psychiatric
contact has been associated with greater stability of BPD diagnosis at follow-up, and
hence, poorer prognosis (Links and van Reekum 1993). Other predictors of poor
prognosis include history of childhood sexual abuse and incest ((Paris 1993); (Stone
1990) and comorbidity with other Axis I and Axis II disorders (Skodol, Oldham et al.
1999);(Links, Heslegrave et al. 1998).
Marzeno et . found that significantly more BPs consulted a psychiatric unit during
childhood than normal controls. Levinson found that among 1,709 adolescents a 1% had
of BP and a 5.7% that did not meet the criteria had at least one distinct mood elevation.
This group with mood elevation had increased levels of anxiety and dysthymia.
Dysthymics (Klien), adolescent cyclothymics and adolescent Bipolar IIs (Levinson) have
been found to have greater social impairment and increased stress than MDDs. In their
analysis of longitudinal findings from the NIMH Collaborative Study data-base, Akiskal
et al found that temperamental measures of mood lability and energy-activity, as well as
phobic anxiety, interpersonal sensitivity and atypical features all served as powerful
predictors of BPII switching among depressed patients that were unipolar at entry
(Akiskal, Maser et al. 1995).
Among adult depressives treatment induced hypomania is the most common
etiology. Those with hyperthymic temperament are thought to be more susceptible to
proceed to BP. Cassano found 10% of a total of 687 depressives with no other
comorbidities had hyperthymic temperament. This group was similar to BPII in gender
distribution and family history but resembled major depressive disorder in course. 60%
of this group developed BPII and 20% experienced mania. This is much higher than the
5-20% conversion rate of unipolar depression to BP (Blacker). The fact that Cassano's
study was a retrospective chart review where evaluators were not blind to the eventual
outcome could have exaggerated the conversion rate. In fact Zerssen et al who used
blinded direct interviews found that most Bipolar IIs resulted from a 'melancholic'
depression and that most hyperthymic i.e. 'manic' depressives developed BPI, perhaps
these 'melancholic depressives would overlap with the dysthymic depressives. Most
treatment emergent bipolar patients rapid cycle. 7.1-8.6% of depressives experience
hypomania (Akiskal and Coryell) and 3.9% have frank mania (Akiskal). Of those who
convert 90% develop spontaneous hypomania after 3-4 years of follow up (Akiskal). Of
note most recent studies find a predominance of women among treatment induced bipolar
IIs with percentages as high as 86% (Cassano).
SUMMARY (ETIOLOGY):
Most BPD stems from an unstable, abusive childhood that leads to the
development of hostile relationships and the constant fear of abandonment. In turn, this
results in impulsivity and affective instability, symptoms which are similar to, yet
qualitatively distinguishable from those in BPII. Most BPIIs seem to inherit an unstable
affect, which initially manifests as depression or a chronic mood disorder but progresses
to full blown hypomania and depression, the secondary consequence of which can lead to
social problems similar to but milder than those seen in BPDs. Thus, the etiology of each
disorder supports hypothesis I.
BPII seems to be a part of a lifelong spectrum that is thought to begin in
childhood with hyperactivity (Ramana-YEAR?) and progress to non-pathologic mood
variations (Weiss-YEAR?), developing into a predisposing cyclothymic, dysthymic or
hyperthymic temperament (Akiskal-YEAR?) and finally BPII. A small fraction of BPII
patients can progress further into BPI (Coryell-YEAR?). Alternatively, childhood
depression (Blacker-YEAR?) or adult depression (Cassano-YEAR?) can develop into
BPII, with a majority of switches among the latter being treatment induced. A higher
percentage of childhood depressives than adult depressives develop bipolar disorder
(Blacker-YEAR?), which is consistent with the finding that depressed children have an
even gender ratio, increased irritability, familial affective loading and substance abuse
(Akiskal-YEAR?).
TREATMENT
Pharmacological
The overlap between drugs reported to be effective in the treatment of BPD and
BP, particularly bipolar disorders characterized by mixed affective episodes and rapid
cycling, point to a common underlying pathophysiology. Akiskal and others
conceptualize BPD as a rapidly cycling variant of BPII (Akiskal, Hantouche et al. 2003),
thus helping to explain the efficacy of mood stabilizers in both groups of patients (Stein,
Simeon et al. 1995). Evidence suggests that affective instability is linked to other
borderline symptoms such as inappropriate anger, self-harm, emptiness and identity
disturbances, so treatments alleviating affective instability might alleviate these other
symptoms as well (Reich, Zarini, Bieri 2009). However, while affective stability in
BPDs and BPIIs is frequently achieved with aggressive use of mood stabilizers, it is
rarely maintained over time with high relapse rates. Further research is required in this
area, as the absence of any known naturalistic studies hampers our ability to appreciate
the extent to which these medications alter the natural course of the disorder. Moreover,
when analyzing treatment response, most studies of bipolars include those with both
Bipolar I and II and fail to break down depression and hypomania into narrower
symptoms, making a dimensional analysis difficult.
Depressed borderline patients also have a poorer response to antidepressants than
patients with Major Depressive Disorder (Cole, Salomon et al. 1984) (Soloff, George et
al. 1989). Very few placebo-controlled medication trials have been conducted for BPD,
but one double-blind placebo-controlled study using fluoxetine found little difference
between treatment and placebo (placebo response was high), with treatment superior to
placebo on only two of five measures--depression and anger (Salzman, Wolfson et al.
1995). Another study found that adding fluoxetine to an effective psychosocial treatment
for BPD (DBT Therapy) provided no added benefit (Simpson, Yen et al. 2004). Patients
with comorbid MDD and BPD, however, appear to do well on fluoxetine, with BPD
patients showing as much improvement after six months on fluoxetine as non-BPD
patients with MDD (Joyce, Mulder et al. 2003).
Response to medications has been the foundation of the inter-axial dimensional
models (Soloff P. H. 1998) and should therefore help elucidate some important aspects of
the relationship between these two Axis I and Axis II disorders. The pharmacological
data, however, are limited by the paucity of large, long-term, randomized, double blind,
and controlled studies as well as the lack of standardized diagnostic methods, dosing
schedules or measures of response to treatment. To date, there have been no head to head
comparisons of treatment options for the two disorders.
In his 1994 review, Soloff found that BPD had many comorbities and was too
heterogeneous for any one drug to treat. According to Soloff, BPDs had an ambiguous
response to medications for three reasons. First, medically unresponsive behavioral
symptoms were rarely separated from reversible biological symptoms. When response
to medicines was ascertained, there was bias towards seeing a lack of response. (Soloff,
Lis et al. 1994). Second, due to emotional instability, compulsive care seeking, and the
occasional use of medicines as weapons (Gunderson 1986), BPDs were poor candidates
for outpatient pharmacotherapy. Finally, since most patients were started on medications
in the acute hospital setting, it is possible that they responded to treatments for comorbid
Axis I disorders. Soloff thus concluded that the dimensional model was not supported by
the results of borderline studies because of the poor efficacy of medications and the
simplicity of the model itself. Most studies of BPDs were cross sectional, and the few
longitudinal studies available did not show any sustained effects of pharmacology.
Cognitive abnormalities
Pharmacological theory seems to support a common cognitive domain for the two
disorders. The cognitive domain is thought to be mediated by the dopaminergic system
and to respond to neuroleptics. Evidence for this was noted in the increased cognitive
disorganization seen in a group of patients on amytriptilline (Soloff P. H. et al. 1989) and
in a group of BPDs who experienced transient psychosis after receiving an amphetamine
challenge (Schulz, Cornelius et al. 1988). In a recent study of Borderlines, symptoms of
dissociation responded to Dialectical Behavior Therapy (Bohus, Haaf et al. 2000).
Affective instability
The affective domain, which includes depression and hypomania, has been
postulated to be mediated by the adrenergic and cholinergic systems. Most mood
stabilizers were efficacious in treating BPIIs, but their effect on BPD was weak and did
not provide proof for the sub affective cyclothymic temperament in BPD as endorsed by
some (Akiskal 1996). However, the fact that antipsychotics and carbazemepine, which
controlled irritability, also resulted in depression, while anti-depressants such as TCAs
resulted in behavioral dyscontrol, leaves the question of affective instability in BPDs
unresolved.
BPII depression responded better to SSRIs and MAOIs than TCAs, and this was
expected since it is often of the atypical subtype. However, the effect of SSRIs and
MAOIs on borderline 'depression' was poor, primarily affecting impulsivity rather than
mood (Gunderson and Phillips 1991). In a direct comparison, phenelzine was more
efficacious in BPDs with comorbid atypical depression than pure BPDs or pure unipolar
atypical depressives. Antipsychotics were as effective as most antidepressants in treating
BPD depression. Mood stabilizers have had greater effect on impulsivity than mood.
Most importantly, in six studies on the treatment of rapid cycling Bipolar disorder with
divalproex, comorbid BPD negatively affected depression but not hypomania (Calabrese
1996). Overall, studies show that BPD 'depression' does not respond to the medications
that are successful in treating BPII or unipolar depression, and therefore suggest that it is
phenomenologically similar to, but biologically distinct from, atypical depression.
To date, there have been no double blind, randomized controlled trials involving
only BPII subjects. Furthermore, most studies have been observational or retrospective in
design. Despite these limitations several findings are worth mentioning. Lithium has
been the best studied treatment, and severalfindings are noteworthy. Lithium was similar
to carbamazepine in one sample of patients including 57 BPIIs, with a trend (not
significant) favoring carbamazepine (Greil and Kleindienst 1999). In one study, lithium
treatment reduced the risk of recurrence of bipolar symptoms by almost six-fold, as well
as hospitalizations, time spent ill, and number of illness episodes per year (Tondo,
Baldessarini et al. 1998). Slow discontinuation of lithium treatment for bipolar disorder
has been found to be associated with reduced risk of morbidity (Baldessarini, 1997).
For long-term treatment, lamotrigine is the only agent with demonstrable efficacy
in a double-blind RCT. In a sample of 324 BPI and BPII subjects, lamotrigine was
statistically superior to placebo in producing stability of symptoms without relapse at six
months (46% lamotrigine versus 18% placebo). In a retrospective study of a sample of
35 bipolar patients with comorbid BPD, it was found that dimensions of borderline
personality improved significantly with treatment and corresponded with response of
bipolar symptoms. There was a trend for comorbid bipolar patients to require a second
medication in addition to lamotrigine during extended treatment (Preston, Marchant et al.
2004).
For short-term treatment there is some evidence for the efficacy of risperidone in
the treatment of hypomanic symptoms. In an open study of 44 BPIIs, 73 % responded to
risperidone according to YMRS scores (Vieta, Gasto et al. 2001). While both hypomanic
and depressive symptoms benefited from risperidone as measured by recurrences,
protection was better for hypomania than for depression. For the treatment of depressive
symptoms, fluoxetine, divalproex and venlafaxine have been shown to be effective in
several trials. A study of 89 BPIIs matched with an equal number of unipolars (n=89)
showed a 50% reduction in Ham-D scores with fluoxetine treatment for both groups, with
a trend toward earlier reduction of symptoms in BPII. There was no significant
difference in relapse rates between the two groups (Amsterdam, Garcia-Espana et al.
1998). An open label study of fluoxetine showed a low manic switch rate of BPII MDE
in a recent study of 37 patients, suggesting that SSRI monotherapy may be a safe and
effective initial treatment of BPII MDE. Studies of Venlafaxine and divalproex using
much smaller sample sizes showed a similar overall efficacy of these medications for
both BPII and unipolar depressive symptoms, with a more rapid reduction of Ham-D
symptoms for BPIIs (Amsterdam 1998); (Amsterdam and Garcia-Espana 2000).
For Borderlines, dialectical behavioral therapy (DBT) has been found effective in
multiple studies, producing improvements in ratings of depression, dissociation, anxiety
and global stress, as well as a significant decrease in the number of parasuicidal acts
(Bohus, Haaf et al. 2000). Adding fluoxetine to dialectical behavior therapy in the
treatment of BPD did not provide any additional benefit in a study of 20 Borderlines
(Simpson, Yen et al. 2004). For depressed patients with BPD, however, fluoxetine seems
to be as effective in alleviating depressive symptoms as it is for depressed patients
without BPD (Fava, 1994; (Joyce, Mulder et al. 2003). In contrast, depressed BPD
patients treated with nortriptyline did not do as well compared to either those treated with
fluoxetine or those without BPD treated with either fluoxetine or nortriptyline (Joyce,
Mulder 2003). Fluoxetine has been found to have significant anti-aggressive effects in
impulsive aggressive individuals with personality disorders, consistent with the above
findings (Coccaro, 1997).
To date, the largest double-blind placebo controlled trial to look at the efficacy of
SSRIs in the treatment of BPD showed that these drugs had a significant effect on mood
lability but no effect on anger or impulsivity. The SSRI used was fluvoxamine, and the
authors of the study suggest that the low dosage used (150mg/day) may have accounted
for the lack of effect on either anger/impulsivity measures.
Several studies have supported the efficacy of atypical antipsychotics (Schulz,
1999; Zanarini, 2001) in the treatment of some symptoms of BPD: impulsivity,
aggression, self-injurious behavior, and affective instability.
Depressive
symptomatology, on the other hand, does not seem to respond to antipsychotics. Older
trials with the typical antipsychotics found them to be beneficial in the short-term only.
Trials with the newer atypical antipsychotics have included olanzapine, clozapine,
risperidone and quetiapine. Olanzapine has been the best studied (Schulz, 1999;
Zanarini, 2001; Bogenschutz, 2004). A placebo-controlled trial of 28 female Borderlines
found that, compared to placebo, olanzapine improved symptoms on all measures
(interpersonal sensitivity, anxiety, hostility, anger, paranoia) except for depression
(Zanarini, 2001). A follow-up placebo-controlled trial that included both male and
female subjects (N=40) found similar results, namely improvement in borderline
symptoms compared to placebo as early as four weeks after starting treatment
(Bogenschutz, 2004). Aripiprazole, moreover, appears to be an effective and relatively
safe agent in the long-term treatment of patients with BPD. In fact, it produced
significant changes according to most scales of the symptom checklist (SCL-90-R),
Hamilton depression rating scale (HDRS), Hamilton anxiety rating scale (HARS), and on
all scales of the state-trait anger expression inventory (STAXI) (Nickel MK et al. 2006)
(Nickel MK et al. 2007). Carbamazepine has been found to be effective for the
treatment of mood instability (Gardner, 1986), anxiety and impulsivity among
Borderlines, and an open trial of valproate has also been shown to be effective (Stein,
1995). Antiepileptic drugs like divalproex have also been widely used to treat
Borderlines, with mounting evidence for their efficacy (Townsend, 2001; Hollander,
2001; Frankenburg, 2002). In addition to divalproex, lamatrogine has been studied in
small samples and has shown some promise, but further, larger scale studies are
necessary (Pinto, 1998). A recently completed trial that warrants further study found that
omega-3 fatty acids might be effective in improving borderline symptoms as well
(Zanarini and Frankenburg 2003).
Impulsivity
Angry outbursts, violent behaviour and suicidality, which belong to the impulsive
domain, have been associated with low CSF 5-HIAA and altered serotonin activity. The
efficacy of anti-convulsants and antidepressants in controlling borderline impulsivity
suggests that it is a phenomenon that corresponds to BPII mood changes. The response
of impulsivity to SSRIs and lithium has been seen in other disorders (Soloff PH,1994),
and was seen in BPDs with wide variability in the treatment response. MAOIs and anticonvulsants also decreased impulsivity. Among BPIIs the SSRIs acted mainly as an
antidepressant whereas lithium acted as a mood stabilizer. In the only study that used
valproate in both BPD and bipolar patients, agitation was the symptom that responded
most.
Anxiety
Soloff speaks of a fourth domain, that of anxiety, which responds to anxiolytics
(Soloff P.H. 2000). Anxiolytics can both decrease anxiety and increase disinhibition.
While anxiety is relieved in BPIIs it is less responsive in BPD where the disinhibitive
function predominates. This raises the possibility that whereas BPII anxiety is
biologically driven and pharmacologically treatable, BPD anxiety is behaviorally driven
and medication resistant.
Overall, the pharmacological responsiveness of BPD is much weaker than that of
BPII. While the results support links in certain areas, such as impulsivity and cognitive
abnormalities, they weaken the connections in others, such as depression and anxiety.
Once again Hypothesis III seems most likely.
Psychotherapy
Psychotherapy is aimed at modifying deeply ingrained, maladaptive interactions
in BPDs (Siever), and has long been the treatment of choice for these patients. Longterm treatment of BPD tends to result in milder cluster C traits (anxious cluster)
(Gunderson 1994), with patients exhibiting more mature, adaptive defenses (Perry). High
expressive emotionality, more enduring psychosocial triggers, greater need for
medication compliance, a greater need for acceptance by the family (Mikowitz), more
financial problems, and frequent interpersonal losses (Soloff) are the main reasons for
psychotherapy.
Unlike in BPDs, psychotherapy alone is never indicated for BPIIs (Expert Group).
Furthermore, milder BPII symptoms (Expert Panel) and more difficulties at home
(Soloff) and at work (Coryell) make BPIIs better candidates for psychotherapy than BPIs.
Psychotheraputic treatments in bipolar disorders have been studied in controlled trials. A
cognitive- behavioral treatment strategy has been shown to help educate patients about
bipolar disorder and its treatment options, teach cognitive-behavioral skills for coping
with psychosocial stressors, facilitate compliance with treatment, and monitor recurrence
of symptoms. Ongoing trials of outpatients, interpersonally oriented psychotherapy for
individuals, and a family-focused psychoeducational treatment, also known as behavioral
family management, suggest that high patient retention rates over the first years of
treatment and family-focused interventions held in an inpatient setting may help some
accept their illness, identify stressors and aversive family interactions, and manage stress
(Hilty et al. 1999).
Cognitive-behavioral approaches to the treatment of borderline patients place
emphasis on observable behaviors and on the psychic schemata or “inner scripts,”
habitual patterns of thought concerning the self and the interpersonal world, but up during
one’s developmental years. The behaviors and their underlying schemata have, in the
evolution of BPD, become maladaptive due to a variety of causative factors: hereditary
predispositions, humiliations and other psychological hurts experienced at the hands of
caretakers, and in some cases outright trauma stemming from physical or sexual abuse.
Important themes relevant to BPD patients include fear of abandonment,
conviction of unlovability and exaggerated guilt. As noted in the discussion of dynamic
approaches, the cognitive distortions typical of BPD patients involve polarized all-ornone attitudes, which Beck refers to as “dichotomous thinking”. Therapy focuses on
decreasing the tendency to dichotomous thinking by helping patients develop better
control over their emotions and impulses, and by strengthening their sense of identity
(Stone M. H. 2006).
The efficacy of psychotherapy in BPDs is debatable. Psycho analytic and insight
oriented therapy show high levels of drop out usually after negative therapeutic reactions.
However uncontrolled studies such as the Meninger study found improvements in ego
strength. Year-long studies of parasuicidal BPDs in Dialectical Behavior Therapy
showed significantly lower attrition rates than treatment as usual. Both the cognitive
behavioral DBT and time limited group therapy are more structured and less emotionally
demanding on care givers and diminishes care seeking behaviors (Gunderson 1994).
Two new interpersonal therapies are becoming useful: Behavioral Family
Management Therapy, which had a nine month relapse rate of 11% compared to 61%
without therapy, and Interpersonal and Social Rhythm Therapy, which results in
stabilization of patients five to six months after discharge (Mikowitz YEAR?). Studies
suggest that BPs, more than unipolars, and perhaps BPIIs more than BPIs, benefit from
psychotherapy.
A controlled outcome study for BPD known as the Personality Disorder
Institute/Borderline Personality Disorder Research Foundation randomized control trial
(PDI/BPDRF RCT) is currently underway to examine the efficacy of three alternative
treatments: a) Transference-focused Psychotherapy, a treatment based on objectrelational and psychoanalytic principles that emphasizes interpretation of object relations
(Clarkin, 1999) b) Dialectical Behavior Therapy (Linehan, Heard et al. 1993), a
commonly used treatment that has been shown to be efficacious (Linehan, Armstrong et
al. 1991) and c)supportive psychotherapy, another object-relational and
psychoanalytically based treatment which places emphasis on the development of a
collaborative engagement with the patient to foster identity development (Rockland,
1992).
Longitudinal studies of personality disorders have also demonstrated that
problems in Borderlines’ interpersonal relationships can be persistent despite
improvements in other symptoms. (Skodol AE 2008). However, for long term gains in
social and interpersonal functioning among Borderlines it appears that completion of a
psychoanalytically oriented partial hospitalization program was superior to standard
psychiatric care (Bateman and Fonagy 2001). Social competence can be taught through a
combination of problem solving therapy plus psychoeducation, which instructs patients
with PDs on how to identify solutions to day to day interpersonal issues (Huband et al
2007). In a randomized controlled trial by Huband et al, participants who received
problem-solving therapy plus psychoeducation showed “significant improvement in
social problem-solving ability, higher social functioning, and reduced anger expression,
compared with control subjects.” More recently, DBT has been recommended for
bipolars as well because of their impulsivity and affective instability (Mikowitz). A
recent study of 50 female BPD patients showed that DBT therapy improved a number of
psychopathological symptoms, including depression, anxiety, interpersonal functioning,
social adjustment, global psychopathology and self-mutilation. A drawback of this study,
however, was that stability of recovery was not assessed after one month following
discharge (Bohus, Schmahl et al. 2004).
Despite successful psychotherapy outcomes with regards to management of both
disorders, psychotherapy has not been found to alter the natural course of either BPD or
BPII. Hence DBT seems the most useful in both groups, and a link in the cognitive
behavioral realm becomes plausible. Hypothesis II therefore seems more likely than the
other two. It is also likely that long-term psychotherapy would make the diagnostic
differentiation between the two disorders more accurate. A recent study evaluated the
cost-effectiveness of cognitive behavior therapy plus treatment as usual compared to
treatment as usual alone for borderline patients, and the results are that the use of
cognitive therapy for BPD does not appear to demonstrate any significant cost-effective
advantage (Palmer S et al. 2006).
It appears, moreover, that in Axis II disorders, particularly borderline personality
disorder, several different types of psychosocial interventions are associated with
reductions in suicidal behaviour (McMain S 2007). Intensive psychosocial treatment
enhances relationship functioning and life satisfaction among patients with bipolar
disorder. Alternate interventions focused on the specific cognitive deficits of individuals
with bipolar disorder may be necessary to enhance vocational functioning after a
depressive episode. (Miklowitz DJ et al. 2007)
Mood Stabilizers
Venlafaxine, tegerteol
Lithium
Lamotrrigine
(Lithium)
Target Sxs
Affective
lability
Impulsivity
Impulsivity
BPII
Conclusion
50%
60%
80%
Sxs
Treated
Affective
lability
Impulsivity
Bipolar
symptoms
BPD
Conclusion
50%
50%
Reduction
risk of recurrence
of symptoms
(Lamotrigine)
Lamictal
Dimensions
Borderline
personality
Improvement Bipolar
symptoms
Production
stability of
symptoms
Depressive
symptoms
Limited
response
50%
Antidepressants
-SSRIs
(Venlafaxine)
-MAOIs
TCAs
Bupropion
(
Atypical
Antipsychotics
(Clozapine)
(Olanzapine)
(Risperidone)
(Quetiapine)
Seroquel
Naltrexone(Opioid
receptor antagonist)
BDZ
CBT
Dialectical Behavior
Therapy
Family Therapy
Depressive
symptoms
Interpersonal Improvement Affective
sensitivity,
instability
anxiety,
hostility,
anger,
paranoia
except for
depression
50%
Dissociative
symptoms
Anxiety
Depression,
dissociation,
anxiety,
global stress
Reduction
Not shown
Not shown
Not effective
Mainstay
treatment
Anxiety
Impulsivity
and
affective
instability
50%
Can be effective
but together with
medications
Cognition
BPII
 Impairments in attention
BPD
 Impairments in attention
 Dissociation-based on
childhood trauma
 Micropsychotic episodes
 Recurrent, brief
depression (RBD)
 Anxiety-more intense,
triggered by pessimistic
worry of future, passive
avoidant behaviors
 Mood cycle: hours, no
symptom free periods
Affect
 Euphoric hypomania
 Discrete major depressive
episodes
 Anxiety-defense
mechanisms related to
isolation, undoing,
intellectualization
 Mood cycle: four days,
have symptom free
periods
Behavior
 Impulsivity-carefree,
uninhibited, stimulus
seeking
 Completed suicides
Etiology
 Non-traumatic life stress
 Childhood trauma/neglect
 Strong genetic inheritance  Biological
 Biological
evidence:inconclusive,
evidence:inconclusive
5HT mechanisms
 Impulsivity-aggression,
irritability
 Repeated self-harm
(parasuicidality)
SUMMARY: Treatment
Response to medications has been the foundation for the inter-axial dimensional
models (Soloff) and should therefore help elucidate important aspects of the relationship
between these two Axis I and Axis II disorders. Both BPD and BPII patients are
characterized by affective lability, which may account for the efficacy of mood stabilizer
treatments in both disorders (Henry et al.), but in BPD these medications have had greater
effect on impulsivity than mood. Lithium treatment, for example, reduces the risk of
recurrence of bipolar symptoms (Tondo et al.) and appears to be especially helpful in
BPDs because it reduces impulsivity. Lamotrigine is also effective in producing stability
of symptoms in BPI and BPII subjects, but one study showed that at doses of 200mg/day
or above bipolar patients present intrusive, repetitive phrases and other obsessional
symptoms ( Kemp DE et al.). In bipolar patients with comorbid BPD the dimensions of
borderline personality and bipolar symptoms can improve significantly. Antidepressants
are effective for the treatment of depressive symptoms in BPIIs but can potentially
worsen mood stability (low manic switch rate of BPII MDE). In BPDs, antidepressants
may play an important role but response to treatment is limited. Several studies support
the efficacy in BPD of atypical antipsychotics in the treatment of some symptoms:
interpersonal sensitivity, anxiety, hostility, anger, paranoia (except for depression), while
in BPII they are used mainly as mood stabilizers. In BPD impulsivity is treated with
mood stabilizers, while naltrexone seems to reduce dissociative symptoms. BDZ are
generally not indicated for BPD due to risk of dependence. Anxiolytics can both
decrease anxiety in BPIIs and increase the disinhibition that predominates in BPDs.
While remission is possible with medication alone in the case of BPII, it has not
been demonstrated in BPD patients. The mainstay of treatment for Borderlines is still
DBT, which has been shown to improve a number of psychopathological symptoms.
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Questions:Should I discuss BDNF?